4.5 Article

Network Organization Is Globally Atypical in Autism: A Graph Theory Study of Intrinsic Functional Connectivity

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ELSEVIER
DOI: 10.1016/j.bpsc.2016.07.008

Keywords

Autism spectrum disorder; Brain networks; Community structure; Graph theory; Intrinsic functional connectivity; Rich club

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Funding

  1. National Institutes of Health [R01-MH081023]
  2. National Institutes of Health/National Institute for General Medical Sciences Initiative for Maximizing Student Development [5R25GM058906-13]

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BACKGROUND: Despite abundant evidence of brain network anomalies in autism spectrum disorder (ASD), findings have varied from broad functional underconnectivity to broad overconnectivity. Rather than pursuing overly simplifying general hypotheses (i.e., under vs. over), we tested the hypothesis of atypical network distribution in ASD (i.e., the participation of unusual loci in distributed functional networks). METHODS: We used a selective high-quality data subset from the Autism Brain Imaging Data Exchange (including 111 ASD and 174 typically developing participants) and several graph theory metrics. Resting state functional magnetic resonance imaging data were preprocessed and analyzed for the detection of low-frequency intrinsic signal correlations. Groups were tightly matched for available demographics and head motion. RESULTS: As hypothesized, the Rand index (reflecting how similar network organization was to a normative set of networks) was significantly lower in participants with ASD compared with typically developing participants. This was accounted for by globally reduced cohesion and density but increased dispersion of networks. While differences in hub architecture did not survive correction, rich club connectivity (among the hubs) was increased in the ASD group. CONCLUSIONS: Our findings support the model of reduced network integration (i.e., connectivity within networks) and differentiation (or segregation; based on connectivity outside network boundaries) in ASD. While the findings were applied at the global level, they were not equally robust across all networks and in one case (i.e., greater cohesion within ventral attention network in ASD) even reversed.

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